Small Intestinal Resident Eosinophils Maintain Gut Homeostasis Following Microbial Colonisation

Abstract

SUMMARYIntestinal homeostasis following postnatal microbial colonization requires the coordination of multiple processes including the activation of immune cells, cell-cell communication, the controlled deposition of extracellular matrix, and epithelial cell turnover and differentiation. The intestine harbors the largest frequency of resident eosinophils of all homeostatic organs, yet the functional significance of eosinophil recruitment to this organ has long remained enigmatic. Eosinophils are equipped to both respond to, and modify, their local tissue environment and thus are able to regulate the adaption of tissues to environmental changes. We report a critical role for eosinophils in regulating villous structure, barrier integrity and motility in the small intestine. Notably, the microbiota was identified as a key driver of small intestinal eosinophil activation and function. Collectively our findings demonstrate a critical role for eosinophils in facilitating mutualistic interactions between host and microbiota and provide a rationale for the functional significance of their early life recruitment in the small intestine.HIGHLIGHTSThe microbiota is a critical regulator of eosinophil activation and turnoverEosinophils uphold intestinal barrier integrity following microbial colonizationLoss of eosinophils at steady-state results in increased villous blunting and altered intestinal motility

The aryl hydrocarbon receptor contributes to tissue adaptation of intestinal eosinophils in mice

“…Intestinal eosinophils upregulated ECM components such as collagens and laminins, as well as matrix metalloproteases. This indicates that eosinophils remodel the ECM, including the basement membrane, and is in line with a recent preprint article that used proteomics to find substantial changes of the intestinal ECM composition in the absence of eosinophils ( Shah et al, 2021 Preprint ). Several studies found that eosinophils affect the intestinal barrier ( Buonomo et al, 2016 ; Johnson et al, 2015 ; Singh et al, 2019 ).…”

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“…Early studies on eosinophils have mostly focused on their role in clearance of helminths and on their contribution to allergic disorders. Their role in tissue tolerance shown in our study, as well as in a preprint study describing their contribution to the gut physiology (Shah et al, 2021), highlight previously unappreciated eosinophil functions. Mast cells and ILC2s are required for Sv clearance and have been shown to induce eosinophil accumulation (Mukai et al, 2017;Nussbaum et al, 2013).…”

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